Ambroxol dry powder for inhalation use with bronchial target

Abstract

The present invention relates to a preparation for inhalation use in form of dry powder comprising particles of ambroxol and/or hydrochlorides thereof, and at least a pharmaceutically acceptable excipient and/or dispersant wherein at least 85% of said particles has a geometrical diameter from 3 to 5 μm. The present invention further relates to the methods for preparing such composition and uses thereof. The present invention thanks to the very fine particles of dry powder, as above defined, constitutes a composition for inhalation use with optimum performances which, combined with inhaler action, reaches and acts directly on the bronchi or on the damaged respiratory tract. The local action and the quick absorption of the drug guarantee good features of bioavailability. The decrease in dosing Ambroxol with respect to the other existing oral or injectable formulations allows to reach quickly, locally and safely, the therapeutic target.

1 . A pharmaceutical composition for inhalation use in form of dry powder comprising particles of Ambroxol and/or hydrochlorides thereof as single active principle, and at least a pharmaceutically acceptable excipient and/or dispersant wherein at least 85% of said particles of Ambroxol in the composition has a geometrical diameter between 3 and 5 μm. 
     
     
         2 . The composition according to  claim 1  wherein the amount of Ambroxol and/or hydrochlorides thereof per dosage unit is from 1 to 14.9 mg. 
     
     
         3 . The composition according to  claim 1  comprising one or more excipients and/or dispersants and/or glidants. 
     
     
         4 . The composition according to  claim 1  comprising lactose, mannitol, glucose, leucine, valine, magnesium stearate and/or mixtures thereof. 
     
     
         5 . The composition according to  claim 1  comprising 20 to 100%, in particular 20 to 59% or 91 to 100% and 91 to 100% of Ambroxol and/or 41 to 80% of excipients and/or 0 to 9% of dispersant and/or glidant. 
     
     
         6 . The composition according to  claim 1  for use as mucolytic expectorant agent, in particular for use as mucolytic expectorant agent acting directly on the site of the bronchial lesions. 
     
     
         7 . A blister or capsule made of aluminium comprising a composition according to  claim 1  inserted hermetically as single dose, in particular in a self-piercing blister. 
     
     
         8 . A dry dust inhaler device comprising a composition according to  claim 1  or a blister or capsule according to  claim 7 . 
     
     
         9 . The inhaler device according to  claim 8  characterized in that it is activated by the air flow alone due to the aspiration by the patient and/or in that it is able to produce a turbulent flow speed so that, even under lower differential pressure conditions, it succeeds in disaggregating and dispersing drug particles to form inhalable particles. 
     
     
         10 . A method for preparing a composition comprising particles of Ambroxol and/or hydrochlorides thereof as single active principle, and at least a pharmaceutically acceptable excipient and/or dispersant wherein at least 85% of said particles of Ambroxol in the composition has a geometrical diameter from 3 to 5 μm, in form of dry powder
 comprising a first step a) of micronizating ambroxol and/or hydrochlorides thereof by air jet grinding and a second step b) wherein the dry powder obtained in step a) is mixed with one or more pharmaceutically acceptable excipients and/or dispersing agents. 
 
     
     
         11 . A method for preparing a composition comprising particles of Ambroxol and/or hydrochlorides thereof as single active principle, and at least a pharmaceutically acceptable excipient and/or dispersant wherein at least 85% of said particles of Ambroxol in the composition has a geometrical diameter from 3 to 5 μm, in form of dry powder comprising a step wherein an aqueous solution or a hydroalcoholic solution of ethanol ≤20% of ambroxol and/or hydrochlorides thereof is subjected to a spray drying and a second step b) wherein the dry powder obtained in step a) is mixed with one or more pharmaceutically acceptable excipients and/or dispersing agents. 
     
     
         12 . A method for preparing a composition comprising particles of Ambroxol and/or hydrochlorides thereof as single active principle, and at least a pharmaceutically acceptable excipient and/or dispersant wherein at least 85% of said particles of Ambroxol in the composition has a geometrical diameter from 3 to 5 μm, in form of dry powder comprising a step wherein an aqueous solution of ambroxol and/or hydrochlorides thereof and at least a pharmaceutically acceptable excipient is subjected to spray freeze drying. 
     
     
         13 . The method according to  claim 10  further comprising an additional step wherein said dry powder is inserted hermetically in an optionally self-piercing blister or capsule made of aluminium as single dose. 
     
     
         14 . A pharmaceutical composition in form of dry powder for inhalation use in form of dry powder obtainable by means of the method according to  claim 11 . 
     
     
         15 . The pharmaceutical composition for use as defined in  claim 2 . 
     
     
         16 . A blister or capsule made of aluminium comprising a composition according to  claim 14  inserted hermetically as single dose, in particular in a self-piercing blister. 
     
     
         17 . A dry powder inhaler device comprising a composition or a blister or capsule according to  claim 16 .